Role of sPLA2 in Spinal Cord Injury and Demyelination

University Of Louisville, Louisville KY

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Demyelination is a pathological process associated with many CMS diseases including traumatic spinal cord Injury (SCI). The death of oligodendrocytes following SCI results in myelin loss and functional impairment. Given that total phospholipases A2 (PLA2) is upregulated following SCI, SPLA2-IIA is expressed following SCI, and causes central demyelination when injected. It is proposed that SPLA2-IIA released after SCI triggers oligodendrocyte cell death which leads to demyelination and loss of function. Therefore, blocking sPLA2-IIA may represent a novel strategy to prevent demyelination associated with secondary SCI. To further address this issue, injections of sPLA2 will be used to create a model of focal demyelination in the dorsolateral white matter targeting the cervical rubrospinal tract. This model will allow testing of therapeutic strategies against sPLA2-IIA-induced demyelination. This investigation will determine 1) whether SPLA2-IIA- induced focal demyelination results in oligodendrocyte cell death. 2) If so, whether sPLA2 inhibitors can block the death of oligodendrocytes in vitro. 3) Finally, whether inhibitors of sPLA2 can create histological and functional improvement in a clinically relevant contusion model of SCI. [unreadable] [unreadable] [unreadable]